The objective of this project is to obtain knowledge that will be useful in developing rationally-based treatment strategies for assisting smokers to abstain from cigarette smoking, the major cause of lung cancer and a major contributor to cardiovascular disease. The project focuses on female smokers because their rates of initiating smoking and of relapse to smoking after quitting are reported to exceed those of males, and they are vastly under-represented in studies of this type. The project tests the hypothesis that smoking motivation and relapse to smoking after a period of abstinence depend on two primary factors: nicotine addiction and self-medication. Addiction is hypothesized to be related to acute, pharmacologically-based nicotine withdrawal symptoms, while the need for self-medication reflects chronic dysfunctions in personality or temperament. Abstinence symptom persistence and liability of relapse to smoking after quitting are hypothesized to be related to enduring personality characteristics as well as to indices of pharmacological tolerance/dependence. For some smokers, pharmacological tolerance-based factors will be the primary predictors of symptomatology and relapse potential; for others, personality predisposition will be more predictive. Tests of the validity of this hypothesized smoker typology as well as three specific program goals will be undertaken: 1) characterization of individual differences in physiological and psychological responses to short-, intermediate-, and long-term smoking cessation; 2) assessment of individual differences in psychological and physiological responses (heart rate, EMG, multi-site EEG activity) to quantified doses of nicotine; 3) testing of hypotheses relating abstinence symptoms and smoking relapse to individual and gender differences in: physiological activity during resting and stressful conditions; physiological and subjective responses to nicotine and nicotine withdrawal; pre-abstinence salivary cotinine concentrations; smoking history; and self report indices of personality, smoking motivation, and tolerance. Clarifying the long-term effects of smoking abstinence in females will help us understand the biological and psychological mechanisms associated with smoking motivation and relapse. This is important because approximately two-thirds of chronic smokers who attempt to quit smoking relapse within a year of quitting. It is expected that knowledge gained from this research will lead to the development of new techniques for helping smokers quit smoking permanently.